This phase II trial studies how well olaparib and cediranib maleate work in treating patients with ovarian, primary peritoneal, or fallopian tube cancer that has come back after a period of improvement (recurrent). Olaparib and cediranib maleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. To evaluate the association of BROCA-homologous recombination (HR) with the clinical activity of cediranib maleate (cediranib)/olaparib, as measured by progression-free survival (PFS), in women with recurrent platinum-sensitive ovarian cancer. II. To assess the clinical activity of cediranib/olaparib, as measured by objective response, in women with recurrent platinum-resistant ovarian cancer. SECONDARY OBJECTIVES: I. To assess overall survival (OS), objective response, and clinical benefit (stable disease \[SD\] or response \>= 16 weeks) in women with platinum-sensitive ovarian cancer, and PFS, OS, and clinical benefit in women with platinum-resistant ovarian cancer. II. To assess the safety of cediranib/olaparib in women with recurrent platinum-sensitive and -resistant ovarian cancer. III. To evaluate the association of circulating endothelial cells at baseline and day 3 with the clinical activity of cediranib/olaparib, as measured by PFS, in women with platinum-sensitive and -resistant ovarian cancer. IV. To evaluate changes in BROCA-HR status between archival and pre-treatment biopsy samples. V. To evaluate the associate of BROCA-HR with the clinical activity of cediranib/olaparib as measured by PFS, in women with platinum-resistant ovarian cancer. VI. To characterize genomic alteration by whole exome sequencing in women with platinum-sensitive and -resistant ovarian cancer. VII. To identify biomarker signatures that correlate with the clinical activity of cediranib/olaparib in women with recurrent platinum-sensitive and -resistant ovarian cancer, including changes in gene expression or acquired mutations in on-treatment tumor biopsies that are associated with clinical activity, and changes in gene expression or acquired mutations in post-progression biopsies that are associated with clinical resistance. VIII. To explore changes in biomarker signatures and candidate angiogenic markers from pre-treatment to post-progression in women with platinum-sensitive and -resistant ovarian cancer. IX. To evaluate the population pharmacokinetics (PK) of the combination of cediranib and olaparib (tablets) in platinum-sensitive and -resistant ovarian cancer. EXPLORATORY OBJECTIVES: I. To determine the feasibility of a mobile phone application (app) ecediranib-olaparib (eCO) to collect patient-generated blood pressure and symptom data based upon study protocol recommendations. II. Assess patient and health care professional perceived usability and satisfaction of the eCO app (for patients) and of a connected web portal (for health care providers). III. Assess the number of generated alerts to the study team (via the web portal and email "high" alerts) based on pre-determined severity levels. OUTLINE: Patients receive olaparib orally (PO) twice daily (BID) and cediranib maleate PO once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a biopsy of tumor, blood sample collection, multigated acquisition scan (MUGA) or echocardiogram, and computed tomography (CT) scan or magnetic resonance imaging (MRI) scan throughout the study. After completion of study treatment, patients are followed up for 30 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
70
Undergo biopsy of tumor
Undergo blood sample collection
Given PO
Undergo CT scan
Undergo echocardiogram
Undergo MRI scan
Undergo MUGA
Given PO
Ancillary studies
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, United States
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Los Angeles General Medical Center
Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
Keck Medical Center of USC Pasadena
Pasadena, California, United States
Mayo Clinic in Florida
Jacksonville, Florida, United States
Moffitt Cancer Center
Tampa, Florida, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
...and 10 more locations
Progression-Free Survival (PFS) by HRR Status in Platinum-Sensitive Ovarian Cancer
PFS determined per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), where disease progression represents at least a 20% increase in the sum of diameters of target lesions, appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. Homologous recombination repair (HRR) status was measured by the BROCA-HR assay. BROCA-HR is a targeted NGS platform including all known gynecologic cancer susceptibility genes and other DNA repair or related genes as well as a 3100 single nucleotide polymorphism panel to increase coverage for loss of heterozygosity (LOH) analysis. HRR status was associated as a pooled group against PFS using the Kaplan-Meier product-limit estimator with 95% confidence bands derived using Greenwood's formula.
Time frame: Interval from start of treatment to documented disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death from any cause, whichever occurs first, assessed up to 32 months.
Objective Response Rate (ORR) in Platinum-Resistant Ovarian Cancer
Responses determined per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI, where Objective Response (OR) represents either a Complete Response (CR; disappearance of all target lesions) or a Partial Response (PR; at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum diameters); Objective Response (OR) = CR + PR.
Time frame: Up to 32 months
Biomarker Signature Development
Will summarize the distribution of all candidate markers using descriptive statistics and non-parametric tests of their association with patient and disease characteristics. Biomarker profiles will be explored using unsupervised hierarchical clustering of all analytes and patients. The association of each candidate marker to progression-free survival will be evaluated by Cox proportional hazard models using a two-sided alpha = 0.05, while estimating the false discovery rate for any sets of identified markers by the Benjamini-Hochberg step-up procedure.
Time frame: Up to 30 days post-treatment
Overall Survival
Will be summarized using the Kaplan-Meier product-limit estimator with 95% confidence bands derived using Greenwood's formula.
Time frame: Up to 1 year
Genetic Alterations
Will be detected by the BROCA-homologous recombination assay. Descriptive statistics will be used to summarize the genetic alterations detected by the BROCA-homologous recombination assay and Bioinformatics Pipeline. The prevalence of each genetic alteration will be reported overall, and within stratum defined by platinum-sensitive and platinum-resistant disease using binomial exact 95% confidence intervals. The primary analysis will associate BRCA mutations (germline or somatic) and other homologous recombination gene mutation (as a pooled group) with/against progression-free survival as a time-to-event endpoint, using Kaplan-Meier product-limit estimates and stratified logrank test using a two-sided alpha of 0.05.
Time frame: Baseline
Change in Circulating Endothelial Cells/Circulating Endothelial Precursor Cells
Will determine if there is an association between levels of circulating endothelial cells at baseline, or the change in circulating endothelial cells from baseline to day 3, and progression-free survival in patients receiving cediranib maleate/olaparib trial, and to determine if there are significant changes from baseline to day 3 in the levels of circulating endothelial cells. Will use a paired t-test. In addition, if the paired differences in values are not normally distributed (p \< 0.05 by a Shapiro-Wilk test), then a Wilcoxon signed rank test will be used instead of a paired t-test.
Time frame: Baseline to day 3
Prevalence of Genetic Alteration Using Whole Exome Sequencing
The prevalence of each genetic alteration will be reported overall, and within platinum-sensitive and platinum-resistant cohorts using binomial exact 95% confidence intervals. Exploratory analyses will associate alterations of a single-gene against progression-free survival as a time-to-event endpoint, using Kaplan-Meier product-limit estimates and logrank test using a nominal two-sided alpha of 0.05.
Time frame: Baseline
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